Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance
dc.contributor.author | Baron, MG | |
dc.contributor.author | Mintram, KS | |
dc.contributor.author | Owen, SF | |
dc.contributor.author | Hetheridge, MJ | |
dc.contributor.author | Moody, John | |
dc.contributor.author | Purcell, WM | |
dc.contributor.author | Jackson, SK | |
dc.contributor.author | Jha, Awadhesh | |
dc.date.accessioned | 2017-03-10T15:44:03Z | |
dc.date.available | 2017-03-10T15:44:03Z | |
dc.date.issued | 2017-01-03 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.other | ARTN e0168837 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/8605 | |
dc.description.abstract |
At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay. Of the pharmaceuticals tested, propranolol, diclofenac and phenylbutazone were metabolised by trout liver spheroids; atenolol, metoprolol, diazepam and carbamazepine were not. Substrate depletion kinetics data was used to estimate intrinsic hepatic clearance by this spheroid model, which was similar for diclofenac and approximately 5 fold higher for propranolol when compared to trout liver microsomal fraction (S9) data. These results suggest that liver spheroids could be used as a relevant and metabolically competent in vitro model with which to measure the biotransformation of pharmaceuticals in fish; and propranolol acts as a reproducible positive control. | |
dc.format.extent | e0168837-e0168837 | |
dc.format.medium | Electronic-eCollection | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Public Library of Science (PLoS) | |
dc.subject | Animals | |
dc.subject | Atenolol | |
dc.subject | Biotransformation | |
dc.subject | Carbamazepine | |
dc.subject | Diazepam | |
dc.subject | Diclofenac | |
dc.subject | Drug Evaluation, Preclinical | |
dc.subject | Female | |
dc.subject | Kinetics | |
dc.subject | Liver | |
dc.subject | Metoprolol | |
dc.subject | Models, Animal | |
dc.subject | Oncorhynchus mykiss | |
dc.subject | Phenylbutazone | |
dc.subject | Propranolol | |
dc.subject | Tandem Mass Spectrometry | |
dc.subject | Water Pollutants, Chemical | |
dc.subject | Xenobiotics | |
dc.title | Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance | |
dc.type | journal-article | |
dc.type | Journal Article | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000391612300058&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 1 | |
plymouth.volume | 12 | |
plymouth.publication-status | Published | |
plymouth.journal | PLOS ONE | |
dc.identifier.doi | 10.1371/journal.pone.0168837 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Admin Group - REF | |
plymouth.organisational-group | /Plymouth/Admin Group - REF/REF Admin Group - FoSE | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/School of Biomedical Sciences | |
plymouth.organisational-group | /Plymouth/Faculty of Science and Engineering | |
plymouth.organisational-group | /Plymouth/Faculty of Science and Engineering/School of Biological and Marine Sciences | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA06 Agriculture, Veterinary and Food Science | |
plymouth.organisational-group | /Plymouth/Research Groups | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED) | |
plymouth.organisational-group | /Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR | |
plymouth.organisational-group | /Plymouth/Research Groups/Marine Institute | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
plymouth.organisational-group | /Plymouth/Users by role/Researchers in ResearchFish submission | |
dc.publisher.place | United States | |
dcterms.dateAccepted | 2016-11-17 | |
dc.identifier.eissn | 1932-6203 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1371/journal.pone.0168837 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-01-03 | |
rioxxterms.type | Journal Article/Review | |
plymouth.funder | Moving up a dimension: 3D in vitro models as effective alternatives to live fish studies::BBSRC | |
plymouth.oa-location | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168837 |